Immunogenicity and Safety Trial of the HIV-1 Tat Vaccine (ISS T-002)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Barbara Ensoli, MD, Istituto Superiore di Sanità
ClinicalTrials.gov Identifier:
NCT00751595
First received: September 11, 2008
Last updated: August 8, 2014
Last verified: August 2014
  Purpose

The study is a randomized, open label, phase II clinical trial directed at evaluating the immunogenicity (as a primary end-point) and the safety (as a secondary end-point), of the recombinant HIV-1 Tat vaccine in HIV-1 infected adult subjects, anti-Tat antibody negative, HAART-treated with chronic suppressed HIV-1 infection, CD4+ T cell counts >= 200 cells/microliter, levels of plasma viremia < 50 copies/ml in the last 6 months prior to the screening and without a history of virologic rebound. The immunogenicity of 3 or 5 immunizations of the two different vaccine doses (7.5 and 30 micrograms) of the Tat vaccine will be evaluated.


Condition Intervention Phase
HIV Infections
Biological: Tat protein
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Open Label, Immunogenicity and Safety Trial of the Vaccine Based on the Recombinant Biologically Active HIV-1 Tat Protein in Anti-Tat Negative HIV-1 Infected HAART-treated Adult Subjects.

Resource links provided by NLM:


Further study details as provided by Istituto Superiore di Sanità:

Primary Outcome Measures:
  • Humoral and cellular immune responses to Tat [ Time Frame: up to 144 weeks ] [ Designated as safety issue: No ]
    It will be measured by the induction, magnitude and persistence of the humoral and cellular immune responses to Tat and by comparing the immunogenicity of a 3/5 immunizations of the different vaccine doses, 7.5 microg and 30 microg


Secondary Outcome Measures:
  • The Secondary Endpoint will be focused on adverse events, including any significant change in hematological/biochemical laboratory parameters. [ Time Frame: up to 144 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 168
Study Start Date: September 2008
Study Completion Date: December 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM A (Tat Protein 7.5 or 30 microg 5X)
Group I: Subjects receiving 5 intradermal immunization with Tat (7.5 microg); Group II: Subjects receiving 5 intradermal immunization with Tat (30 microg).
Biological: Tat protein
Biologically active recombinant Tat protein
Experimental: ARM B (Tat Protein 7.5 or 30 microg, 3X)
Group I: Subjects receiving 3 intradermal immunization with Tat (7.5 microg); Group II: Subjects receiving 3 intradermal immunization with Tat (30 microg)
Biological: Tat protein
Biologically active recombinant Tat protein

Detailed Description:

This phase II clinical trial is directed at evaluating the immunogenicity and the safety of the HIV-1 Tat protein-based vaccine. Anti-Tat antibody negative, HIV-1 positive subjects treated successfully with HAART will be screened and recruited for a 48-weeks study, including a period of 16 or 8 weeks treatment phase and a period of 32 or 40 weeks follow-up phase, in arm A or Arm B, respectively. One hundred sixty-eight subjects will be randomized 1:1:1:1 to one in 2 arms (Arm A and Arm B) and each arm will be divided in the following groups:

Arm A - Group I: 5 immunizations with Tat (7.5 microg) at weeks 0, 4, 8, 12, 16; Arm A - Group II: 5 immunizations with Tat (30 microg) at weeks 0, 4, 8, 12, 16; Arm B - Group I: 3 immunizations with Tat (7.5 microg) at weeks 0, 4, 8; Arm B - Group II: 3 immunizations with Tat (30 microg) at weeks 0, 4, 8.

Four vaccination regimens will be tested by intradermal administration of the Tat vaccine at two different doses (7.5 microg or 30 microg) in 5 or 3 immunizations.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-55 years
  • Anti-Tat antibody negative subjects
  • HIV-1 infected subjects under successful HAART treatment with HIV plasma viremia < 50 copies/ml in the last 6 months prior to the screening
  • Subjects with any pre-HAART CD4 nadir;
  • CD4+ T cell counts ≥ 200 cells/μl at enrolment;
  • Availability for the planned study duration
  • Negative pregnancy test for women of childbearing potential (to be performed during the screening phase and just before the immunizations) and use of an acceptable mean of contraception (condom, hormonal or mechanical methods) for one month prior to immunization and for the all duration of the study
  • Signed informed consent

Exclusion Criteria:

  • Concomitant AIDS-related opportunistic disease;
  • Concomitant neoplastic diseases;
  • History of malignant neoplastic diseases [NOTE: Subjects with history of non malignant neoplastic diseases completely resolved according to the fulfillment of all the specific recovery criteria, in agreement with the current guidelines in medical oncology are eligible];
  • History of encephalopathy, neuropathy or unstable CNS pathology, immunodeficiency, autoimmune disease, angina or cardiac arrhythmias, or any other clinically significant medical problems;
  • Any evidence, as judged by the investigator, of unstable cardio-vascular disease (e.g. unstable hypertensive disease needing modification or introduction of an anti-hypertensive treatment);
  • Chest radiography showing evidence of active or acute cardiac or pulmonary disease within 6 months prior to study screening visit;
  • History of anaphylaxis or serious adverse reactions to vaccines as well as serum IgE levels exceeding 1000 U.I./ml;
  • History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g. Steven-Johnson syndrome, bronchospasm, or hypotension);
  • Active tuberculosis documented PPD skin test within one year [NOTE: if the PPD skin test is positive, then a chest x-ray will be done and if no findings consistent with active pulmonary tuberculosis and no indications exist for prophylaxis or treatment, the subject is eligible for participation in this trial];
  • Medical or psychiatric condition which preclude subject compliance with the protocol. Specifically, persons with psychotic disorders, major affective disorders, suicidal ideation are to be excluded;
  • Current use of psychotropic drugs prescribed for major psychotic disorders;
  • Concomitant participation in any experimental study;
  • Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
  • Live attenuated vaccines within 60 days of study inclusion [NOTE: Medically indicated sub-unit or killed vaccines (e.g., influenza, pneumococcal, hepatitis A and B) are not exclusionary, but should be given at least 4 weeks away from HIV immunizations];
  • Receipt of blood products or immunoglobulin in the past year;
  • Previous participation in an HIV-1 vaccine trial (subjects who despite their participation as placebo in a HIV-1 vaccine trial have never been effectively administered with a HIV-1 vaccine are eligible);
  • Drug and/or alcohol abuse;
  • Use in the last 6 months or concomitant use of anti CCR5 inhibitors and/or integrase inhibitors and/or fusion inhibitors;
  • Pregnant or lactating women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00751595

Locations
Italy
San Gerardo Hospital
Monza, Milan, Italy, 20052
General Hospital of Bari
Bari, Italy, 70124
Spedali Civili di Brescia
Brescia, Italy, 25123
General Hospital-University of Ferrara
Ferrara, Italy, 44100
A.M. Annunziata Hospital
Florence, Italy, 50012
S.M. Goretti Hospital
Latina, Italy, 04100
San Raffaele Hospital
Milan, Italy, 20127
L. Sacco Hospital
Milan, Italy, 20152
General Hospital-University of Modena
Modena, Italy, 41100
San Gallicano Hospital
Rome, Italy, 00144
Amedeo di Savoia Hospital
Torino, Italy, 10149
Sponsors and Collaborators
Barbara Ensoli, MD
Investigators
Study Director: Barbara Ensoli, MD, PhD National AIDS Center (CNAIDS), Istituto Superiore di Sanita', Rome, Italy
  More Information

Additional Information:
Publications:

Responsible Party: Barbara Ensoli, MD, MD, PHD, Istituto Superiore di Sanità
ClinicalTrials.gov Identifier: NCT00751595     History of Changes
Other Study ID Numbers: ISS T-002
Study First Received: September 11, 2008
Last Updated: August 8, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Istituto Superiore di Sanità:
HIV
Tat protein
Therapeutic vaccine
HAART
HIV Therapeutic Vaccine
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 23, 2014